Alexis Hermida1,2,3, Véronique Fressart1,2, Francoise Hidden-Lucet1,2, Erwan Donal4, Vincent Probst5, Jean-Claude Deharo6, Philippe Chevalier7, Didier Klug8, Nicolas Mansencal9, Etienne Delacretaz10, Pierre Cosnay11, Patrice Scanu12, Fabrice Extramiana1,13, Dagmar I Keller14, Stephanie Rouanet15, Philippe Charron1,9, Estelle Gandjbakhch1,2. 1. Centre de Référence Pour les Maladies Cardiaques Héréditaires, APHP, Hôpital de la Pitié Salpêtrière, Paris, France. 2. Sorbonne Universités, UPMC Université Paris 6, Assistance Publique-Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, ICAN, Département de Cardiologie, Paris, France. 3. Service de Rythmologie, Centre Hospitalo-Universitaire, Amiens, France. 4. Département de Cardiologie, Hôpital Pontchaillou, Rennes, France. 5. Institut du Thorax, Centre Hospitalo-Universitaire, Nantes, France. 6. Département de Cardiologie, Centre Hospitalo-Universitaire, Marseille, France. 7. Département de Cardiologie, Centre Hospitalo-Universitaire, Lyon, France. 8. Département de Cardiologie, Centre Hospitalo-Universitaire, Lille, France. 9. AP-HP, Groupe Hospitalier Ambroise Paré, UVSQ, INSERM U1018, CESP, Boulogne, France. 10. Service de Cardiologie, Hôpital de L'Ile, Berne, Switzerland. 11. Département de Cardiologie, Centre Hospitalo-Universitaire, Tours, France. 12. Département de Cardiologie, Centre Hospitalo-Universitaire, Caen, France. 13. Département de Cardiologie, Centre Hospitalo-Universitaire Bichat-Claude-Bernard, Paris, France. 14. Emergency Department, University Hospital Zurich, Zurich, Switzerland. 15. Statistic Unit - StatEthic, Levallois-Perret, France.
Abstract
BACKGROUND: Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. METHODS AND RESULTS: Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2 patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). CONCLUSIONS: In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.
BACKGROUND: Previous studies suggested that genetic status affects the clinical course of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients. The aim of this study was to compare the outcome of desmoglein-2 (DSG2) mutation carriers to those who carry the plakophilin-2 (PKP2) mutation, the most common ARVC/D-associated gene. METHODS AND RESULTS: Consecutive ARVC/D patients carrying a pathogenic mutation in PKP2 or DSG2 were selected from a national ARVC/D registry. The cumulative freedom from sustained ventricular arrhythmia and cardiac transplantation/death from heart failure (HF) during follow-up was assessed, compared between PKP2 and DSG2, and predictors for ventricular arrhythmia and HF events determined. Overall, 118 patients from 78 families were included: 27 (23%) carried a DSG2 mutation and 91 (77%) a PKP2 mutation. There were no significant differences between DSG2 and PKP2 mutation carriers concerning gender, proband status, age at diagnosis, T-wave inversion, or right ventricular dysfunction at baseline. DSG2patients displayed more frequent epsilon wave (37% vs. 17%, P = 0.048) and left ventricular dysfunction at diagnosis (54% vs. 10%, P < 0.001). During a median follow-up of 5.6 years (2.5-16), DSG2 and PKP2 mutation carriers displayed a similar risk of sustained ventricular arrhythmia (log-rank P = 0.20), but DSG2 mutation carriers were at higher risk of transplantation/HF-related death (log-rank P < 0.001). The presence of a DSG2 mutation vs. PKP2 mutation was a predictor of transplantation/HF-related death in univariate Cox analysis (P = 0.0005). CONCLUSIONS: In this multicentre cohort, DSG2 mutation carriers were found to be at high risk of end-stage HF compared to PKP2 mutation carriers, supporting careful haemodynamic monitoring of these patients. The benefit of early HF treatment needs to be assessed in DSG2 carriers.
Authors: Anneli Svensson; Pyotr G Platonov; Kristina H Haugaa; Wojciech Zareba; Henrik Kjærulf Jensen; Henning Bundgaard; Thomas Gilljam; Trine Madsen; Jim Hansen; Lars A Dejgaard; Lars O Karlsson; Anna Gréen; Bronislava Polonsky; Thor Edvardsen; Jesper Hastrup Svendsen; Cecilia Gunnarsson Journal: Cardiology Date: 2021-09-01 Impact factor: 1.869
Authors: Nadine Lubos; Svenja van der Gaag; Muhammed Gerçek; Sebastian Kant; Rudolf E Leube; Claudia A Krusche Journal: Basic Res Cardiol Date: 2020-06-12 Impact factor: 17.165